Perhaps more than any other “-omics” endeavor, the accuracy and level of detail obtained from mapping the major connection pathways in the living human brain with diffusion MRI depends on the capabilities of the imaging technology used. The current tools are remarkable; allowing the formation of an “image” of the water diffusion probability distribution in regions of complex crossing fibers at each of half a million voxels in the brain. Nonetheless our ability to map the connection pathways is limited by the image sensitivity and resolution, and also the contrast and resolution in encoding of the diffusion probability distribution. The goal of our Human Connectome Project (HCP) is to address these limiting factors by re-engineering the scanner from the ground up to optimize the high b-value, high angular resolution diffusion imaging needed for sensitive and accurate mapping of the brain’s structural connections. Our efforts were directed based on the relative contributions of each scanner component. The gradient subsection was a major focus since gradient amplitude is central to determining the diffusion contrast, the amount of T2 signal loss, and the blurring of the water PDF over the course of the diffusion time. By implementing a novel 4-port drive geometry and optimizing size and linearity for the brain, we demonstrate a whole-body sized scanner with Gmax = 300mT/m on each axis capable of the sustained duty cycle needed for diffusion imaging. The system is capable of slewing the gradient at a rate of 200 T/m/s as needed for the EPI image encoding. In order to enhance the efficiency of the diffusion sequence we implemented a FOV shifting approach to Simultaneous MultiSlice (SMS) EPI capable of unaliasing 3 slices excited simultaneously with a modest g-factor penalty allowing us to diffusion encode whole brain volumes with low TR and TE. Finally we combine the multi-slice approach with a compressive sampling reconstruction to sufficiently undersample q-space to achieve a DSI scan in less than 5 minutes. To augment this accelerated imaging approach we developed a 64-channel, tight-fitting brain array coil and show its performance benefit compared to a commercial 32-channel coils at all locations in the brain for these accelerated acquisitions. The technical challenges of developing the over-all system are discussed as well as results from SNR comparisons, ODF metrics and fiber tracking comparisons. The ultra-high gradients yielded substantial and immediate gains in the sensitivity through reduction of TE and improved signal detection and increased efficiency of the DSI or HARDI acquisition, accuracy and resolution of diffusion tractography, as defined by identification of known structure and fiber crossing.

Imaging biomarkers derived from magnetic resonance imaging (MRI) data are used to quantify normal development, disease, and the effects of disease-modifying therapies. However, motion during image acquisition introduces image artifacts that, in turn, affect derived markers. A systematic effect can be problematic since factors of interest like age, disease, and treatment are often correlated with both a structural change and the amount of head motion in the scanner, confounding the ability to distinguish biology from artifact. Here we evaluate the effect of head motion during image acquisition on morphometric estimates of structures in the human brain using several popular image analysis software packages (FreeSurfer 5.3, VBM8 SPM, and FSL Siena 5.0.7). Within-session repeated T1-weighted MRIs were collected on 12 healthy volunteers while performing different motion tasks, including two still scans. We show that volume and thickness estimates of the cortical gray matter are biased by head motion with an average apparent volume loss of roughly 0.7%/mm/min of subject motion. Effects vary across regions and remain significant after excluding scans that fail a rigorous quality check. In view of these results, the interpretation of reported morphometric effects of movement disorders or other conditions with increased motion tendency may need to be revisited: effects may be overestimated when not controlling for head motion. Furthermore, drug studies with hypnotic, sedative, tranquillizing, or neuromuscular-blocking substances may contain spurious “effects” of reduced atrophy or brain growth simply because they affect motion distinct from true effects of the disease or therapeutic process.

We introduce a novel method of prospectively compensating for subject motion in neuroanatomical imaging. Short 3D EPI volumetric navigators (vNavs) are embedded in a long 3D sequence, and the resulting image volumes registered to provide an estimate of the subject’s location in the scanner at a cost of less than 500 ms, ~ 1% change in contrast, and ~ 3% change in intensity. This time fits well into the existing gaps in sequences routinely used for neuroimaging, thus giving a motion-corrected sequence with no extra time required. We also demonstrate motion-driven selective reacquisition of k-space to further compensate for subject motion. We perform multiple validation experiments to evaluate accuracy, navigator impact on tissue intensity/contrast, and the improvement in final output. The complete system operates without adding additional hardware to the scanner and requires no external calibration, making it suitable for high-throughput environments.

The engineering of a 3T human MRI scanner equipped with 300 mT/m gradients – the strongest gradients ever built for an in vivo human MRI scanner – was a major component of the NIH Blueprint Human Connectome Project (HCP). This effort was motivated by the HCP’s goal of mapping, as completely as possible, the macroscopic structural connections of the in vivo healthy, adult human brain using diffusion tractography. Yet, the 300 mT/m gradient system is well suited to many additional types of diffusion measurements. Here, we present three initial applications of the 300mT/m gradients that fall outside the immediate scope of the HCP. These include: 1) diffusion tractography to study the anatomy of consciousness and the mechanisms of brain recovery following traumatic coma; 2) q-space measurements of axon diameter distributions in the in vivo human brain and 3) postmortem diffusion tractography as an adjunct to standard histopathological analysis. We show that the improved sensitivity and diffusion-resolution provided by the gradients is rapidly enabling human applications of techniques that were previously possible only for in vitro and animal models on small-bore scanners, thereby creating novel opportunities to map the microstructure of the human brain in health and disease.

Data quality is increasingly recognized as one of the most important confounding factors in brain imaging research. It is particularly important for studies of brain development, where age is systematically related to in-scanner motion and data quality. Prior work has demonstrated that in-scanner head motion biases estimates of structural neuroimaging measures. However, objective measures of data quality are not available for most structural brain images. Here we sought to identify quantitative measures of data quality for T1-weighted volumes, describe how these measures relate to cortical thickness, and delineate how this in turn may bias inference regarding associations with age in youth. Three highly-trained raters provided manual ratings of 1840 raw T1-weighted volumes. These images included a training set of 1065 images from Philadelphia Neurodevelopmental Cohort (PNC), a test set of 533 images from the PNC, as well as an external test set of 242 adults acquired on a different scanner. Manual ratings were compared to automated quality measures provided by the Preprocessed Connectomes Project's Quality Assurance Protocol (QAP), as well as FreeSurfer's Euler number, which summarizes the topological complexity of the reconstructed cortical surface. Results revealed that the Euler number was consistently correlated with manual ratings across samples. Furthermore, the Euler number could be used to identify images scored "unusable" by human raters with a high degree of accuracy (AUC: 0.98-0.99), and out-performed proxy measures from functional timeseries acquired in the same scanning session. The Euler number also was significantly related to cortical thickness in a regionally heterogeneous pattern that was consistent across datasets and replicated prior results. Finally, data quality both inflated and obscured associations with age during adolescence. Taken together, these results indicate that reliable measures of data quality can be automatically derived from T1-weighted volumes, and that failing to control for data quality can systematically bias the results of studies of brain maturation.

The Human Connectome Projects in Development (HCP-D) and Aging (HCP-A) are two large-scale brain imaging studies that will extend the recently completed HCP Young-Adult (HCP-YA) project to nearly the full lifespan, collecting structural, resting-state fMRI, task-fMRI, diffusion, and perfusion MRI in participants from 5 to 100+ years of age. HCP-D is enrolling 1300+ healthy children, adolescents, and young adults (ages 5–21), and HCP-A is enrolling 1200+ healthy adults (ages 36–100+), with each study collecting longitudinal data in a subset of individuals at particular age ranges. The imaging protocols of the HCP-D and HCP-A studies are very similar, differing primarily in the selection of different task-fMRI paradigms. We strove to harmonize the imaging protocol to the greatest extent feasible with the completed HCP-YA (1200+ participants, aged 22–35), but some imaging- related changes were motivated or necessitated by hardware changes, the need to reduce the total amount of scanning per participant, and/or the additional challenges of working with young and elderly populations. Here, we provide an overview of the common HCP-D/A imaging protocol including data and rationales for protocol decisions and changes relative to HCP-YA. The result will be a large, rich, multi-modal, and freely available set of consistently acquired data for use by the scientific community to investigate and define normative developmental and aging related changes in the healthy human brain.

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In population groups where head pose cannot be assumed to be constant during a magnetic resonance spectroscopy examination or in difficult-to-shim regions of the brain, realtime volume of interest, frequency, and shim optimization may be necessary. We investigate the effect of pose change on the B 0 homogeneity of a (2 cm) 3 volume and observe typical first-order shim changes of 1 mT/m per 1°rotation (chin down to up) in four different volumes of interest in a single volunteer. An echo planar imaging volume navigator was constructed to measure and apply in real-time within each pulse repetition time: volume of interest positioning, frequency adjustment, and first-order shim adjustment. This volume navigator is demonstrated in six healthy volunteers and achieved a mean linewidth of 4.4 Hz, similar to that obtained by manual shim adjustment of 4.9 Hz. Furthermore, this linewidth is maintained by the volume navigator at 4.9 Hz in the presence of pose change. By comparison, a mean linewidth of 7.5 Hz was observed, when no correction was applied. Single voxel spectroscopy (SVS) relies on a homogeneous B 0 , a consistent frequency, and assumes that the localization remains valid for the duration of the scan. For a restless subject, who is unable to maintain a consistent pose during the scan, these do not hold true. We present a method that provides real-time (once every pulse repetition time [TR]) B 0 and frequency measurements in addition to real-time correction of the volume of interest (VOI) position.Current motion and artifact correction methods in magnetic resonance spectroscopy can be divided into two categories: phase and frequency adjustments and localization correction. Phase and frequency adjustments refer to a group of techniques that measure the signal phase and frequency by using either the residual water signal (1-4) or a secondary navigator (5-7). These methods correct both a velocity-induced phase error and frequency changes that result from either scanner drift or pose change. Phase and frequency adjustments can be applied both retrospectively and prospectively, but only prospective methods are able to correct the change in water saturation frequency.Localization correction techniques in magnetic resonance spectroscopy have been demonstrated using an optical tracking system (7) and an imaging navigator technique called PROspective MOtion correction (PROMO) (8). The technique presented by Zaitsev et al. (7) provides both frequency and localization correction by combining optical tracking with navigator based frequency correction in addition to reacquisition of free induction decays (FIDs) with velocity induced phase errors. The disadvantages of an optical device are that they require: additional hardware, a marker to be rigidly affixed to the head, a clear line of sight between camera and marker, and the calibration of a camera to scanner transform.There are several navigator-based motion tracking methods available, which take advantage of the k-space properties of rigid body transforms to subsample ks...